One of the most frequent pathologies that affects the venous system of the Western population is represented by the venous insufficiency, and nowadays it is estimated that more than 60% of the adult population suffers from this problem.
The most common manifestation of this pathology is varix. This term indicates the dilation, the tortuous course of the superficial veins, the valve insufficiency with a related reflux, whose appearance is mainly referable to intrinsic anomalies of the vein wall, high intraluminal pressure, structural and functional vein changes.
Although varicose veins constitute a benign pathology, they can be accompanied by two kinds of serious complications: ulceration and thrombophlebitis. The ulceration occurs usually near the ankle and, generally, in cases of particularly extended varices, while the thrombophlebitis consists of the presence of thrombi, real plugs constituted initially by platelets and fibrin, to which red corpuscles are added later inside the vein, together with an inflammatory response of the vein wall. The complication of the thrombophlebitis is pulmonary embolism, that expresses itself with clinical pictures of different seriousness, up to death.
The therapy for the varicose disease, proposed today, follows four kinds of approach: pharmacological, elastic compressive, surgical subdivided into classical or endovascular and sclerotherapeutic.
In particular, the endovascular surgery has been recently standing out, because of its less invasive character, and the sclerotherapy, that lives a new era with the arrival of the foams. The sclerotherapy consists of injecting into the varix a sclerosing substance which causes the lumen closure and consequently, disappearance of the varix, followed by application of an elastic compressive brace (stocking or bandage). This method is getting more and more attention from medicine.
Four variables must be taken into consideration, in order to make the sclerosis efficient:
1) the drug must have high destructive power on the endothelium and possibly also on the subendothelial structures and at the same time be gentle to other vasal and perivascular structures and further it should not have significant systemic side effects
2) it must get in contact with as much of endothelial surface as possible
3) the concentration of the drug must remain as stable as possible in the injection place and/or in the place of contact with the vein wall,
4) the contact time must be sufficient to determine the damage. At present, the sclerotherapy is commonly carried out by injecting a sclerosing drug in liquid form, or a so-called sclerosing foam, a preparation, in which the active substance having foaming capability is first subjected to a turbulence by energetic shaking, that creates micro bubbles (30-100 micron diameter) structured foam or mousse constituted substantially by gas, internally, and by foam active substance, that forms the outer surface of the bubble, for example of drug: sodium tetradecilsulphate or polydocanol.
The diluting effect due to the circulation can be considered a consequence on one hand positive, since it limits the risks of a progressive and uncontrolled sclerosis, on the other hand negative, because the dilution influences the sclerosis efficacy.
The sclerosis with foam or mousse has overcome successfully the dilution problem: the mousse (micro-bubbles of gas and drug) does not mix with a liquid, and, once injected into vein, it is capable of displacing the blood and coming in contact with venous endothelium more easily, improving the sclerosing effect (a better immediate and distant result appears from the literature). Therefore, it behaves as an almost solid substance and actually, it is a dynamic fluid aggregate of bubbles.
This has allowed reducing the dose of drug being used and its concentration (thus, we would expect a smaller number of complications, but actually the exact opposite effect appears from the literature: a larger number of side effects and new side effects).
Actually, it has been noted that the injected micro-bubbles get into the circulation and are subjected to the venous circulation effect, which is extremely variable at the lower limbs level, due to the system complexity, and moreover, it is difficult to predict its flow directions. Therefore, the micro-bubbles can reach the deep venous circulation, thrombosis of the deep veins, and inevitably, end up in the lung and the systemic circulation, thus causing side effects (headache, visual alterations, constriction in the chest), even potentially serious (stroke).
Consequently, in order to try to enhance the sclero-mousse methodology efficacy, some devices have been conceived and produced, substantially catheters, which are capable of better controlling the sclerosing foam location, the contact time of the drug with the vein wall, its effect and possible side effects.
A first device of this kind is a direct catheter, which is used for injecting the sclerosing foam at the desired point and along the whole venous axis, during the catheter distal end withdrawal. With this catheter, it is possible to control the place and the quantity of the injected drug (echo-sclerosis), however it is not possible to control a series of events: 1) the dilution caused by the blood flow that disperses the bubbles 2) the effective contact of the drug with the whole wall, for the same reason 3) the contact time, for the same reason 4) getting into the circulation, for the same reason.
Currently, other typologies of catheters are known: a two-way catheter with a distal balloon that allows to better control the sclerosing foam injected into the vessel through outlet holes, situated near the balloon, holes that allow sucking the foam out of the vessel through the same catheter afterwards. Another one, still with a distal balloon, but having many holes along the catheter axis, so as to distribute uniformly the drug in the part of the vein to be treated.
Also these two catheters are not completely free from some limits. The first device does not ensure a uniform concentration of the drug (foam) along the entire section of vessel to be sclerosed. The concentration decreases as one moves away from the balloon, that is from the outlet hole. Consequently, the varicose vein treated section will get in contact with a more and more diluted drug (foam), as one moves away from the outlet hole. It is confirmed by the fact that during the foam suction step, a mixture of foam/drug and blood is constantly recovered.
Moreover, because of the necessity to carefully inject quantities of foam not bigger than 6-10 cc, the initial volume of the varicose vein to be treated can influence even considerably the drug/volume ratio inside the vessel and in some cases jeopardize its therapeutic result.
In the second case, with more outlet holes, even if a more homogeneous concentration can be maintained along the whole section of the vein, and a given quantity of drug (for example 8 ml) must be used, standard concentrations of drug cannot be ensured in the section of the vein to be treated, for all kinds of varices.
Thus, all these devices, some more some less, along with the vessel subjected to a sclerosing therapy, constitute an “open system”, that is a system under the influence of the venous circulation, resolve only partially the previously described problems.
In order to obviate such disadvantages, one must take into consideration the necessity to isolate the part of varix to be treated with a double balloon catheter, thus creating a “closed system”, not exposed to the effect of the local venous circulation. Such a “closed system” is composed of the segment of varix under consideration, the catheter present therein, two balloons at the extremities, the blood contained in the isolated and static section of the vein.
The drug, in the form of mousse (stable and constant volume), is injected into such a “closed system”, dislocates, in the small collateral vessels, the blood contained in the system, occupying the entire part of the vein being treated without any dilution.
The characteristic feature of this system is the location of the foam in a closed system, which consequently is not subjected to the local circulation effects, thus resolving the dilution problem.
However, although theoretically this system fulfills the conditions to be considered stable and thus efficient, also such solution has some limits.
Actually, the veins to be treated with the sclerosing foam can have variable dimensions and volume, that can range from a minimum of about 7-10 cm3 to a maximum of 90-120 cm3 and, since one cannot introduce as big quantity of sclerosing foam as desired, so as not to make its effect uncontrollable, for example having to use about 8 ml of foam, to satisfy the treatment of a section of vessel, whose volume varies from 10 cm3 to 100 cm3, it is noticed immediately that in the first case the foam concentration and the volumetric filling of the part of the vein to be treated is high (8:10=80%), while in the second case it is very low (8:100=8%).
This causes a high foam-volume concentration in the first case and a very low one in the second case, with obviously very different final results.
Therefore, disadvantageously, the two-balloon catheters defining a closed system do not allow treating efficaciously big dimensions blood vessels without introducing big quantities of medicine and consequently, risking to lose the control over the treatment.
Moreover, since it is necessary to inject into a closed system with two balloons at the ends, the syringe will require high operating pressure, so as to be able to dislodge the blood in the collateral vessels. This could cause a leakage of the micro-bubbles into the collateral circulation (perforating), before emptying the section of the part of blood, thus increasing the TVP risk.